Cytotoxic, genotoxic, and toxicogenomic effects of heated tobacco products and cigarette smoke in human primary keratinocytes

Autor: Yoshihisa Morishita, Shogo Hasegawa, Shin Koie, Sei Ueda, Satoru Miyabe, Satoshi Watanabe, Mitsuo Goto, Hitoshi Miyachi, Shuji Nomoto, Toru Nagao
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Tobacco Induced Diseases, Vol 20, Iss September, Pp 1-9 (2022)
Druh dokumentu: article
ISSN: 1617-9625
DOI: 10.18332/tid/152510
Popis: Introduction Heated tobacco products (HTPs) appear to be less harmful to health than conventional cigarettes (CCs). However, limited analytical data are available to support this claim. This study aimed to compare the cytotoxic, genotoxic, and toxicogenomic effects of HTPs and CCs in carcinogenesis via multistep gene mutations in the oral mucosal cells. Methods Cigarette smoke extract (CSE) was obtained from HTPs and CCs. Primary human oral keratinocytes (HOKs) were treated with 5% and 20% CSE from HTPs and CCs. Cell survival rate assays were performed after 6, 12, and 24 h. After 6 h, DNA double-strand breaks (DSBs) were evaluated using anti-γH2AX antibodies with immunohistochemistry. mRNAs expressions of mediator of DNA damage checkpoint 1 (MDC1) and ataxia telangiectasia and Rad3-related protein (ATR), were analyzed. Expressions of miR-22 and miR-185 were analyzed because miR- 22 targets MDC1 and miR-185, ATR. Results The HOKs had equivalent survival rates after exposure to the same concentrations of CSE from CCs and HTPs. HTPs increased foci formation of γH2AX in HOKs, as did CCs (without CSE vs 20% HTP, p
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